Bone Marrow Cells in Murine Colitis: Multi-Signal Analysis Confirms Pericryptal Myofibroblast Engraftment without Epithelial Involvement

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P27Kip1, regulated by glycogen synthase kinase-3β, results in HMBA-induced differentiation of human gastric cancer cells

<p>Abstract</p> <p>Background</p> <p>Gastric cancer is the second most common cause of global cancer-related mortality. Although dedifferentiation predicts poor prognosis in gastric cancer, the molecular mechanism underlying dedifferentiation, which could provide fundamental insights into tumor development and progression, has yet to be elucidated. Furthermore, the molecular mechanism underlying the effects of hexamethylene bisacetamide (HMBA), a recently discovered differentiation inducer, requires investigation and there are no reported studies concerning the effect of HMBA on gastric cancer.</p> <p>Methods</p> <p>Based on the results of FACS analysis, the levels of proteins involved in the cell cycle or apoptosis were determined using western blotting after single treatments and sequential combinations of HMBA and LiCl. GSK-3β and proton pump were investigated by western blotting after up-regulating Akt expression by Ad-Akt infection. To investigate the effects of HMBA on protein localization and the activities of GSK-3β, CDK2 and CDK4, kinase assays, immunoprecipitation and western blotting were performed. In addition, northern blotting and RNase protection assays were carried out to determine the functional concentration of HMBA.</p> <p>Results</p> <p>HMBA increased p27Kip1 expression and induced cell cycle arrest associated with gastric epithelial cell differentiation. In addition, treating gastric-derived cells with HMBA induced G0/G1 arrest and up-regulation of the proton pump, a marker of gastric cancer differentiation. Moreover, treatment with HMBA increased the expression and activity of GSK-3β in the nucleus but not the cytosol. HMBA decreased CDK2 activity and induced p27Kip1 expression, which could be rescued by inhibition of GSK-3β. Furthermore, HMBA increased p27Kip1 binding to CDK2, and this was abolished by GSK-3β inhibition.</p> <p>Conclusions</p> <p>The results presented herein suggest that GSK-3β functions by regulating p27Kip1 assembly with CDK2, thereby playing a critical role in G0/G1 arrest associated with HMBA-induced gastric epithelial cell differentiation.</p

Resolution of inflammation: a new therapeutic frontier

Dysregulated inflammation is a central pathological process in diverse disease states. Traditionally, therapeutic approaches have sought to modulate the pro- or anti-inflammatory limbs of inflammation, with mixed success. However, insight into the pathways by which inflammation is resolved has highlighted novel opportunities to pharmacologically manipulate these processes — a strategy that might represent a complementary (and perhaps even superior) therapeutic approach. This Review discusses the state of the art in the biology of resolution of inflammation, highlighting the opportunities and challenges for translational research in this field

A comparison of auditory brainstem responses across diving bird species

© 2015, Springer-Verlag Berlin Heidelberg. There is little biological data available for diving birds because many live in hard-to-study, remote habitats. Only one species of diving bird, the black-footed penguin (Spheniscusdemersus), has been studied in respect to auditory capabilities (Wever et al., Proc Natl Acad Sci USA 63:676–680, 1969). We, therefore, measured in-air auditory threshold in ten species of diving birds, using the auditory brainstem response (ABR). The average audiogram obtained for each species followed the U-shape typical of birds and many other animals. All species tested shared a common region of the greatest sensitivity, from 1000 to 3000 Hz, although audiograms differed significantly across species. Thresholds of all duck species tested were more similar to each other than to the two non-duck species tested. The red-throated loon (Gavia stellata) and northern gannet (Morus bassanus) exhibited the highest thresholds while the lowest thresholds belonged to the duck species, specifically the lesser scaup (Aythyaaffinis) and ruddy duck (Oxyurajamaicensis). Vocalization parameters were also measured for each species, and showed that with the exception of the common eider (Somateriamollisima), the peak frequency, i.e., frequency at the greatest intensity, of all species’ vocalizations measured here fell between 1000 and 3000 Hz, matching the bandwidth of the most sensitive hearing range